In September Omir Santos was called up from the Norfolk tides and was giving number 67. Santos played in 11 games and had 10 at-bats, recording one hit. In that season he caught nine games, starting three.

During the 2010 MLB Winter Meetings, Santos signed a minor league contract with the Detroit Tigers. He was promoted to the Tigers on April 19 and was given number 18 to fill in for injured backup catcher Victor Martínez. On April 19 against the Seattle Mariners Santos got a pinch hit single. The next day he got the start were he went 0 for 4 and caught nine innings.[7] Santos was recalled again in August to replace Miguel Cabrera who was attending the birth of his child. The Tigers used Cabrera's paternity leave as an opportunity for Santos to catch a game in place of Alex Avila, who had started the previous 18 games. Regular backup catcher Víctor Martínez had been limited to designated hitter due to injury.[8]

After being outrighted to Triple-A in 2011, Santos was given an invitation to spring training as a non-roster player. He did not make the opening day roster, but was called up to the Tigers on May 30, 2012 after injuries to Alex Avila and Gerald Laird. On June 2, 2012, Omir Santos had a walk-off sacrifice fly to beat the New York Yankees.[9]

On February 5, 2013 Santos signed a minor league contract with the Cleveland Indians.[12] Santos started the 2013 season with the Triple-A Columbus Clippers, and was called up to the Indians on April 9, 2013.[citation needed] He appeared in one game for the Indians before being optioned back to Columbus a week later. On July 14, Santos was outrighted off the 40-man roster to Columbus.[13]